University of Wisconsin scientists have developed a sensitive, rapid test to detect the presence of the botulinum toxin, the most lethal substance known on earth.
This new discovery could aid in the advancement of new technologies to avert bioterrorist events and may also lay the groundwork for further progress identifying drugs that inhibit the action of the typically fatal toxin.
The researchers, led by UW physiologist Edwin Chapman, published their results in the current issue of the Proceedings of the National Academy of Sciences. The publication includes two new essays for detection of the toxin, one of which is a swift, real-time test that improves on the current method of detection.
According to the Center for Disease Control, there are seven types of botulinum toxin, four of which cause severe illness in humans. On average, approximately 110 cases are reported each year in the United States. Symptoms of botulism include double vision, slurred speech, dry mouth and weakness of muscles eventually leading to paralysis.
Min Dong, a postdoctoral fellow, did much of the research leading to new tests utilizing fluorescent sensors to detect the neurotoxin both in a test tube and in living cells.
To detect the toxin, fluorescent proteins are introduced into the cell. Normal cells glow with fluorescence, but this glow is extinguished when the neurotoxin is introduced.
“The major application of our botox sensors [is] to characterize toxin activity in the laboratory to save animal tests, cost and time to detect toxins,” Dong said in an e-mail. “[The test] also can be used to screen small chemical molecules in very large-scale, both in vitro (in test-tubes) and in living cells. This would lead to the finding of potential drugs that can prevent botox toxicity in humans.”
According to the researchers, the new tests are neither expensive nor difficult to use. The real-time test could be applied in programs to protect our food and water supply, military on the battleground or healthcare workers dealing with unknown agents.
Although infection by the toxin is rare, scientists and government officials acknowledge the toxin’s potential as a bioterrorist threat and are offering more funding to researchers who study botulinum toxin.
“We started this project before [the terrorist attacks of Sept. 11, 2001] happened because we are interested in its scientific [meaning],” Dong said. “It is still of scientific interest to us, but now it has more social attention on our studies, [giving] extra motivation for us to work on these toxins. In addition, there are more funding opportunities than before.”
Chapman agrees that, although somewhat exaggerated, terrorism [by biological agents] is a real threat.
“I think many people are now concerned about nuclear weapons falling into the hands of people that will use them in terrorist acts,” Chapman said.
An antitoxin against botulism is available and maintained by the CDC, although it must be administered during the early stages of the illness to be effective.
Chapman’s interest in such neurotoxins began when he was in college. At that time, no one knew the mechanisms by which the toxins produced their effects. As a postdoctoral student at Yale in 1993, Chapman collaborated with other researchers and determined how two of the neurotoxins functioned. After a 10-year hiatus from toxins, Chapman and the researchers in his lab decided to tackle the many questions they had about the toxins’ mechanism of action.
Chapman, Dong and their fellow-researchers are currently working on the next step — finding receptors for the other six neurotoxins. In theory, the tests should detect all seven types of the neurotoxin. According to Chapman, the Wisconsin Alumni Research Foundation is working on the application of the new tests in public health settings.
